Key Laboratory of Cell Homeostasis and Cancer Research of Guangdong Higher Education Institutes and Affiliated Cancer Hospital & Institute, Guangzhou Medical University, Guangzhou 910095, China.
Key Laboratory for Reproductive Medicine of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 910095, China.
Biomolecules. 2022 May 5;12(5):668. doi: 10.3390/biom12050668.
Liver cancer stem cells (LCSCs) are a small subset of oncogenic cells with a self-renewal ability and drug resistance, and they promote the recurrence and metastasis of hepatocellular carcinoma (HCC). However, the mechanisms regulating LCSCs have not been fully explored. By enriching LCSCs from spheroid cultures and performing transcriptomic analysis, we determined that alanine-glyoxylate aminotransferase (AGXT), which participates in the metabolism of serine and glycine, was significantly upregulated in spheroid cultures, and its function in LCSCs remains unknown. Through the exogenous overexpression or short hairpin RNA knockdown of AGXT in HCC cells, we observed that changes in the AGXT level did not affect the spheroid ability and population of LCSCs. The knockdown of AGXT in LCSCs reduced the number of spheroids and the population of LCSCs; this implies that AGXT is required for the maintenance of cancer stemness rather than as a driver of LCSCs. Mechanistically, AGXT may sustain the self-renewal potential of LCSCs by upregulating the expression of SRY-box transcription factor 2 (SOX2) and octamer-binding transcription factor 4 (OCT4), two well-known master regulators of cancer stemness. Taken together, our study demonstrates the role of AGXT in supporting LCSCs; thus, AGXT merits further exploration.
肝癌干细胞（LCSCs）是一小部分具有自我更新能力和耐药性的致癌细胞，它们促进了肝细胞癌（HCC）的复发和转移。然而，调节 LCSCs 的机制尚未被充分探索。通过从球体培养物中富集 LCSCs 并进行转录组分析，我们确定参与丝氨酸和甘氨酸代谢的丙氨酸-乙醛酸氨基转移酶（AGXT）在球体培养物中显著上调，但其在 LCSCs 中的功能尚不清楚。通过外源性过表达或 HCC 细胞中的短发夹 RNA 敲低 AGXT，我们观察到 AGXT 水平的变化并不影响 LCSCs 的球体形成能力和群体。AGXT 在 LCSCs 中的敲低减少了球体的数量和 LCSCs 的群体；这意味着 AGXT 是维持癌症干性所必需的，而不是 LCSCs 的驱动因素。从机制上讲，AGXT 可能通过上调两个众所周知的癌症干性主调控因子——性盒转录因子 2（SOX2）和八聚体结合转录因子 4（OCT4）的表达，来维持 LCSCs 的自我更新潜力。总之，我们的研究表明了 AGXT 在支持 LCSCs 中的作用；因此，AGXT 值得进一步探索。
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